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Issue 9, 2017
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Cobalt-catalysed reductive C–H alkylation of indoles using carboxylic acids and molecular hydrogen

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Abstract

The direct CH-alkylation of indoles using carboxylic acids is presented for the first time. The catalytic system based on the combination of Co(acac)3 and 1,1,1-tris(diphenylphosphinomethyl)-ethane (Triphos, L1), in the presence of Al(OTf)3 as co-catalyst, is able to perform the reductive alkylation of 2-methyl-1H-indole with a wide range of carboxylic acids. The utility of the protocol was further demonstrated through the C3 alkylation of several substituted indole derivatives using acetic, phenylacetic or diphenylacetic acids. In addition, a careful selection of the reaction conditions allowed to perform the selective C3 alkenylation of some indole derivatives. Moreover, the alkenylation of C2 position of 3-methyl-1H-indole was also possible. Control experiments indicate that the aldehyde, in situ formed from the carboxylic acid hydrogenation, plays a central role in the overall process. This new protocol enables the direct functionalization of indoles with readily available and stable carboxylic acids using a non-precious metal based catalyst and hydrogen as reductant.

Graphical abstract: Cobalt-catalysed reductive C–H alkylation of indoles using carboxylic acids and molecular hydrogen

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Supplementary files

Article information


Submitted
11 May 2017
Accepted
11 Jul 2017
First published
26 Jul 2017

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2017,8, 6439-6450
Article type
Edge Article

Cobalt-catalysed reductive C–H alkylation of indoles using carboxylic acids and molecular hydrogen

J. R. Cabrero-Antonino, R. Adam, K. Junge and M. Beller, Chem. Sci., 2017, 8, 6439
DOI: 10.1039/C7SC02117H

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